NRSC 2110 Blog

Each year, over half a million Americans die from drug use. In a recent study published in Nature Neuroscience, addiction was defined as "a chronically relapsing disorder characterized by a compulsion to seek and take drugs, a loss of control over intake, and the emergence of a negative emotional state during abstinence." But that's not what addiction is, not really. Addiction is a high-speed chase into the depths of human despair. It's no man's land- black, and empty, and unbearable. And relapse is worse. Relapse is the shadows in the darkest corners of human existence. So wouldn't it be great if there were a cure for this relapse monster? Researchers may have found just that.

In a study published in January (http://www.nature.com/neuro/journal/v14/n4/full/nn.2758.html), researchers studied an area of the brain called the ventromedial prefrontal cortex (vmPFC) and its role in reducing context-induced heroin seeking (because we all know that being in a place where you used to shoot up is just as risky as having the needle poised in your veins). In previous studies on cocaine addiction in rodents, activation of the vmPFC inhibited drug relapse. Bossert et al. challenged this idea by identifying a subpopulation of neurons in the vmPFC that increases context-induced heroin-seeking behavior upon activation.

To identify this population of neurons in the vmPFC, scientists used Fos immunohistochemistry to show that reexposure to an environment associated with heroin consumption activated these neurons. The rats were exposed to two contexts: in context 1, rats were trained to self-administer heroin 3 hours per day for 12 days by pressing on a lever. In context 2 (which differed from context 1 in tactile, visual, auditory, and circadian components), rats could still press a lever, but did not receive heroin. Consequently, they eventually stopped pressing the lever. Following the extinction training, rats were reintroduced to either context 1 or 2 and given lever access, although no heroin was supplied.

The most significant finding was that 71% of the neurons recruited by reexposure to context 1 were excitatory glutamatergic neurons (13% were inhibitory GABA neurons). Thus, reexposure to an environment associated with heroin recruits excitatory pyramidal neurons. Most importantly, these neurons are responsible for the learned association between environmental factors and the effects of heroin.

Bossert et al. then used an innovative method to selectively inactivate vmPFC neurons that were activated in the heroin context. A prodrug called Daun02, which decreases cell excitability for several days, was injected into the vmPFC after reexposure to the heroin context. When exposed to context 1 a second time, rats that received the prodrug immediately following reexposure to the context 1 the first time showed a decrease in context-induced activation of vmPFC neurons, AND diminished heroin-seeking behavior.

So why is this important? Researchers have found a neuron population involved in environmentally triggered relapse, and we now know that this population reacts differently for heroin than it does for cocaine. But how promising is this study in the future of addiction? It's quite obvious that just quitting a drug will never keep you safe from the drug itself. But at least we know which neuron population is responsible for the horrific heroin relapse. So instead of going to the methadone clinic, junkies can just get parts of their ventromedial prefrontal cortex lesioned. And if they're addicted to heroin AND cocaine, well then they're really screwed.

That's what bothers me about addiction studies like these: rather than feeling enlightened and hopeful, I feel discouraged and even more in the dark than I was before I read the study. While it's great that 'our knowledge is expanding in the field of addiction,' the plausibility of expanding this study to humans (which are different from genetically engineered rodents), is slim to none. For all their scientific wisdom, researchers could never accurately convey what addiction is. Relapse can't be scientifically treated, because no matter how many neurons you activate or inactivate, the house on the corner can still kill you. Relapse is the razor's edge between life and death, not the number of lever presses inside a cage.

We've all been there. You're standing across from someone animatedly relating a crucial piece of their day to you and five minutes later when you zone back in you realize you haven't heard a word they said. Do you fake it, politely nodding, and hope you won't be asked for your opinion? Do you apologize and ask them to repeat themselves? In school you might have been known as "that kid", always day dreaming and becoming preoccupied with everything other than the lesson at hand. Maybe the last time you were reading a book you couldn't get through a page without watching your neighbor water their lawn or taking an enthusiastic interest in the fly buzzing around the window. You may have been diagnosed with ADD or simply adopted the diagnosis on your own with the rest of our culture as a buzz word for excusing our collective distractibility. Laptops, smart phones, and constant stimulation could make anyone a little scattered. Now, thanks to Neuroscience, you can blame it, along with a host of other things, on your biology. Research published in the Journal of Neuroscience in May of 2011 could even be used to support blaming it on your parents.

People involved in the study were asked to score themselves on their attention spans and ability to focus on their daily tasks. They used a test that has been used to measure distractibility many times before. The density of gray matter in the left superior parietal lobe of those in the study correlated directly with their reports of distractibility. The researchers were able to disrupt activity in the implicated area of the brain using transcranial magnetic stimulation to further test their theory that there is a biological basis for distraction and the ability to ignore it. During the disruption, the people involved in the study became more susceptible to distraction as was expected. By using TMS while subjects were performing a task researchers were able to observe how susceptible the subjects were to outside stimuli while messing with this area of the brain. Researchers were pleased to make a connection between reports of low attention span, biology, and measurable laboratory tests.

Next time you zone out, offer an apology that you can't focus on the conversation at hand because your parietal lobe is giving you trouble and simply won?t filter out the pretty girl who just walked by, the construction in the street, or the smell of coffee wafting it's way through the office, or you could just spring for lunch.

Our society has become a sleep deprived one which has lead researchers to study the effects of it. It has now been accepted that sleep is needed for memory consolidation. Does sleep improve all types of memory? People generally think so but what if a study found that to not be true?

Researchers at Georgetown University and Catholic University have apparently found an exception to this idea of memory consolidation during sleep for motor sequence learning. I found this article to catch my eyes easily as having taken a class on the neurobiology of learning and memory; the researchers were definitely daring to challenge this already accepted idea. They focused their study on implicit consolidation which I found interesting because it seems that dreaming of performing a patterned motor sequence and remembering would help the most.

In their study,(http://www.jneurosci.org/content/27/46/12475.full.pdf+html) the researchers studied 36 right-handed college students at 3 different visits with half of the participants tested in the morning (8am) and half in the evening (8 pm). The morning group had 12 hours of awake-rest between their 1st and 2nd visits and 12 hours of sleep between their 2nd and 3rd visits. The evening group had the opposite, with the sleep full rest first. Also half of the participants were given instructions with mention of the patterned sequences and half were just given minor instructions. In addition, 18 right handed subjects were used as controls and were allowed to sleep in between the 3 testing?s.

For each visit the subjects were given the alternating serial response time task which involved the subjects responding to pushing a button to a target (a filled in circle) that appeared in one of 4 circles that were aligned in a row. The circle stayed filled in until the correct key was pressed. Then another circle filled in and the experiment with 8 warm-up trials and then 80 experimental ones consisting of patterns which alternated with random trials. The researchers also performed cued and probed time trials to differentiate between pattern and random trials. (Note: my explanation of their study might be a bit confusing but that?s because I found theirs not as well explained as it could have been. Unless, of course I went to another study which they directed me to a study with a better description of the methods)

The researchers found that daytime enhancement occurred for overall reaction time but not for pattern specific learning. Speed only improved if the rest period was over the day and not when it was overnight. This seemed very odd to me (which they kind of admitted to) and makes me believe it was poorly constructed. It seems obvious that college kids are going get better after 8 am as most college kids are still asleep at 8. Maybe if they did it at 10 am and 10 pm or if they had to be awake for, say, 2 hours before the test. The results might have been different then.

In the end, I found the title very interesting and it made me want to read the article but I was disappointed. The article wasn?t written as clearly as it should have been and I had a hard time following it. It referred to other papers so many times that I found it distracting. With that fact and the fact that the experiment was poorly conceived, it seemed to me that their experiment didn?t test anything new and that they were just testing what others already have. They also had so many different discussions that that also made the paper rather confusing.

I would have liked to have seen something more than just behavioral testing. For example, it would have been more interesting if they measured the subject?s brain activity during the tasks. More neuroscience testing would have helped make their research stronger. Also, while reading the article, I found myself wondering why studying sleep-dependent consolidation of implicit patterned motor learning is even important. How would that be beneficial to us? I can definitely see the use in researching sleep-dependent consolidation for motor learning in general but why would learning about sleep-dependent consolidation and patterned motor learning exactly help us with our lives? I?m all ears if someone could give me an example to change my mind. Again, I definitely believe research should continue on consolidation and motor learning and I find that fascinating.

The last thing I?m going to note involves their last sentence which they mentioned interpreting implicit consolidation features saying, ?deciphering each component will make it possible to better understand and use off-line (implicit) performance enhancements?. The performance enhancements part slightly bothered me because that brings up a whole can of ethical issues but I?ll save that for another time.